Research institutions registered under the Animal Welfare Act (AWA) are required to submit an annual report to the Animal and Plant Health Inspection Service that details, among other specifications, a listing of the common names and the numbers of reportable species used. In 2017, there were approximately 1,100 research facilities in the USA registered under the requirements of the AWA and reporting the total use of 792,168 regulated animals, including 191,766 guinea pigs, 145,841 rabbits, 98,576 from among a combination of several species of hamsters (the majority being the Syrian variety), 75,825 nonhuman primates, 64,707 dogs, 51,020 pigs, 18,146 domestic cats, 14,045 sheep, and a combination of 132,242 by head-count of various species not otherwise identified. Overall combined annual use of all of these species, with the exception of nonhuman primates, has been in a general pattern of steady decline since 1992.
There are no federal reporting requirements for mice, rats, birds, amphibians, or fish, making precise numbers difficult to determine. Research subjects of these species, for the most part, are obtained via a combination of in-house breeding colonies as well as from commercial vendors, and sometimes collectors, with production and sales data from the latter two being proprietary and not disclosed publicly.
The estimated total number of mice and rats used for research purposes annually in the United States is 20–30 million. There are millions of zebrafish and thousands of amphibians likewise used annually.
The full sequencing of human and a number of animal genomes spawned the concept of precision medicine, with the goal of tailoring treatments for each unique individual as shaped by genetics, environment, and lifestyle and away from the norm of generalizing therapy to the mean of the population. Although they are in developmental infancy, animal model-based, proof-of-precision studies that are reflective of the broad variation in patients suggests roles for a greater diversity of species and genotypes beyond those in conventional use during the current mouse-centric era.
The domestic mouse, Mus musculus and related subspecies, is popular as a mammalian research model because of its small size, short lifespan, adaptability, docility, low husbandry costs, fecundity, and well-defined health and genetic backgrounds. It is also relatively easy to perform genetic manipulation, such as “humanization” with human genes, tumors, immune cells, or components of the microbiome. The development of embryonic genome editing techniques, most prominently the CRISPR-Cas9 system and next-generation prime editing, in the creation of GEM (genetically engineered model) mice has profoundly increased and broadened the utility of mice as research subjects. Spurred by these advances, countless mutant genotypes of mice have been developed and continue to be developed, ranging from subtle defects in immune function to full-fledged, inherited diseases virtually homologous with those of people and other mammals.
Among other rodents, the domestic Norway rat (Rattus norvegicus) is second only to the mouse as a research subject. Rats share many of the attributes of mice that make them attractive for use in research, but because they are larger than mice they are suited for a greater variety of surgical manipulations and are often favored for behavioral studies. Numerous mutant and inbred strains and outbred stocks of rats are used in a broad array of studies, including for aging, cancer, reproductive physiology, drug effects, addiction, alcoholism/cirrhosis, arthritis, brain and nerve injury, hypertension, embryology, teratology, endocrine diseases, neurophysiology, infectious disease, stroke, organ transplantation, and surgically induced disease. The genetic engineering of mutant rat types, however, has lagged behind that of mice and has yet to show effect.
Excluding mice and rats, guinea pigs and rabbits are the most common mammals used in research, although their numbers have declined from peaks in the 1990s. Although the guinea pig (Cavia porcellus) was among the first animals to be used in biomedical research, its applicability has diminished relative to mice and rats due to its long gestation period (59–72 days), small litter size (2–5), poor vascular access, and difficulties in anesthesia. However, they contribute in notable ways to immunology, vaccine and infectious disease research, and as hearing models. Rabbit use in product safety testing has been declining, but they remain valuable in studies of vision, orthopedics, and cardiology.
In addition to the Syrian hamster (Mesocricetus auratus), a few other species of hamsters are used in research, including the Armenian, Siberian (Djungarian), Chinese, European, and Turkish species. Hamsters are readily available, reproduce easily, and are relatively free of spontaneous diseases yet susceptible to many induced viral diseases. They are used for studies of obesity, induced carcinogenesis, prostatic disease, toxicity, infectious diseases (including slow viruses), dental caries, chronic bronchitis, and teratogenesis.
Other rodent species used in research include gerbils, deer mice, chinchillas, cotton rats, rice rats, multimammate rats, spiny mice, degus, voles, and woodchucks, among others.
Although rodent models are unarguably the most common for scientific use, larger animal models provide unique opportunities for biomedical research. Dogs are used in studies of cardiology, endocrinology, orthopedics, prosthetic devices, surgical techniques, pharmacokinetics, and product safety. Since dog use began declining in 1984, livestock of several species have been used more frequently. This has been a consequence of regulatory and public pressure related to the use of dogs, but it is also due to attributes of comparative anatomy and physiology making livestock more conducive to particular investigations. For example, swine are used for cardiovascular research (particularly atherosclerosis), in studies of digestive physiology, as surgical models, and for xenotransplantation. Sheep are used for studies of neonatal development, human vaccine improvement, asthma pathogenesis and treatment, drug delivery, circadian rhythms, and surgical techniques.
Nonhuman primates remain critical to studies of vision, the neurosciences, infectious diseases, vaccines, and product safety testing. In recent years, they have become increasingly valuable as models of immunodeficiency virus infection and the neurodegenerative diseases associated with aging.
Although they have been in steady decline in absolute numbers used in research since 1980, cats are still important models in the neurosciences, consequences of aging, certain inherited diseases, and in the study of infectious diseases.
The most important aquatic species used in research are the zebrafish and the clawed frogs, tetraploid South African Xenopus laevis, and the smaller, diploid, more rapidly maturing X tropicalis, originating from forested West Africa. Each of these species offer advantages in studies of development, while zebrafish are also easily subject to mutation to induce a variety of disease models and in cancer and tissue healing studies. The clawed frogs are valuable in studies of the cell cycle and gene function.